This grant application requests supplementary funds to support our ongoing program of research to explore both the underlying biochemical pathophysiology of the affective disorders as well as the possible mechanisms of action of drugs (and other somatic interventions) used in their treatment. A broad objective of the research is the development of clinically useful biological as well as clinical criteria for classifying the depressive disorders and predicting differential clinical antidepressant responses to various forms of treatment. This research, which will test a number of specific hypotheses (as described in detail in the text of this application), can be subsumed under several broad categories. 1. Studies of pretreatment biological and clinical variables as predictors of response to antidepressant pharmacotherapy. 2. Studies of biological differences (including measures of biogenic amine metabolism and sleep stages) in clinically defined subtypes of depressive disorders. 3. Studies of clinical differences in groupings of depressed patients defined by various biological criteria (including measures of biogenic amine metabolism and $ sleep stages). 4. Studies of the relationships among various biological variables (including measures of biogenic amine metabolism and sleep stages) in patients with depressive disorders.5.Longitudinal studies of the changes in biogenic amine metabolism and sleep stages associated with drug administration or changes in clinical state in patients with depressions or manias.